1. Field of the Invention
This invention discusses useful techniques in the production and recovery of steroids.
2. Description of the Art Practices
The production of progesterone from the corresponding aldehyde via the intermediate step of conversion by acetic anhydride is known. This process is discussed in an article entitled "Progesterone from 3-Acetoxybisnor-5-cholenaldehyde and 3-Ketobisnor-4-cholenaldehyde" by Heyl et al, Volume 72, pp 2617-2619, June, 1950.
In the Heyl et al reference the 3-ketobisnor-4-chlorenaldehyde is converted via acetic anhydride using sodium acetate as a catalyst into the corresponding bisenol and enol acetate. The bisenol acetate and enol acetate are described in the reference as being conveniently ozonized directly to progesterone.
The Heyl et al reference further states that 3-beta-acetoxybisnor-5-cholenaldehyde may also be converted via an ozonolysis step to progesterone. In either reaction the 3-ketobisnor-4-cholenaldehyde which is a 20 steroid carboxaldehyde, will not be fully converted to progesterone. The presence of the unconverted aldehyde in the mixture with progesterone is, of course, undesirable noting that the progesterone is used for human pharmaceutical purposes.
Thus, given the fact that a convenient route for progesterone production exists from a particular 20 steroid carboxaldehyde, it is desirable that such reaction be conducted as efficiently as possible. Of course, as stated above, it is also extremely desirable to minimize the amount of aldehyde which remains in mixture with the progesterone.
It has also been suggested by Herr et al in "Enamine" Derivatives of Steroidal Carbonyl Compounds, JACS; Volume 74, July 20, 1952, pp 3627-3630 that the 3-ketobisnor-4-cholenaldehyde could be converted by a secondary amine such as piperidine through dehydration in the presence of potassium carbonate to give a dipiperidyl compound. Partial degradation of the dipiperidyl compound regenerates piperidine and a compound designated as an "enamine" which is an alpha, beta unsaturated amine of the particular steroid. Through subsequent steps the "enamine" could be converted by ozonolysis to give progesterone. In following the teachings of this reference, as well as the earlier JACS article, it is noted that some unreacted steroid carboxaldehyde will invariably be present in the final mixture containing the progesterone. For the reasons given above, this steroid aldehyde in the final product is undesirable and should be minimized.
Therefore, when the production of progesterone is attempted through either route, it is desirable in view of economy and purity of the end product that the steriod carboxaldehyde be removed from a mixture of that material and the progesterone.
In the present invention, the separation of such steroid carboxaldehydes from progesterone is accomplished and the steroid carboxaldehyde is recovered. The separation is accomplished by converting the steroid carboxaldehyde to the corresponding acetal followed by solvent extraction of the components. The steroid carboxaldehyde is then recycled into the feed material for the progesterone production. While some hemiacetal steroids are known from U.S. Pat. No. 3,264,285 to Borrevang issued Aug. 2, 1966 it is not suggested that acetal formation can be used to increase progesterone production.
Throughout the specification and claims, percentages and ratios are by weight and temperatures are in degrees Celsius, unless otherwise indicated. Numerals preceding the term steroid indicate the position of the named functional group on the steroid.